This invention relates to a process and an apparatus for forming capsules, for example for the delivery of pharmaceuticals, and also to the resulting capsules.
A variety of pharmaceuticals and other materials are delivered in capsules. Where the material is a particulate material such as a powder it may be enclosed in a hard capsule, typically of elongated round-ended cylindrical shape, made in two pieces for assembly around the material. Both liquid and particulate material may be enclosed in soft capsules, these capsules being made from films of a soft elastic polymer which are brought together between rotating dies that have cavities in their surfaces. The material to fill the capsules is supplied between the films as the films deform into the cavities; as the dies move the films come together and are sealed together by application of heat and/or pressure at the dies. Both types of capsules are commonly made from gelatin films. The bonding of thermoplastic polymer films using dielectric heating (or radio frequency heating) has also been known for many years. In this process the two pieces of thermoplastic material are positioned between opposed electrodes (or one electrode and a base plate), the electrodes are pressed together, and a radio frequency voltage is applied between the electrodes. This process is however applicable only to those materials which have a significant dielectric loss index, for example greater than 0.2, over the range say 20-60 MHz, for example polyvinylchloride. Dielectric welding has not hitherto been considered suitable for welding the water-soluble polymers which are desirably used in making capsules for pharmaceuticals.
According to the present invention there is provided a process for making capsules, the process using two films of a water-soluble or digestible polymeric material, and the process comprising the steps of deforming the films to form a multiplicity of recesses between a pair of rotary dies, filling the recesses with a flowable filling material, welding the films together by dielectric welding at the rotary dies to form a multiplicity of enclosures containing the filling material, and separating the filled enclosures from the remaining parts of the films so as to form a multiplicity of capsules.
The rotary dies act as opposed electrodes, to which the high frequency electrical supply is provided. The supply may in principle be at a frequency between 1 MHz and 200 MHz, usually between 10 MHz and 100 MHz, but stringent limits are imposed on any emitted radio waves. In practice therefore the choice of frequency may be more limited. For example the supply frequency may be 27.12 MHz, or 40.68 MHz. Preferably the electrical connections to both the rotary dies are by a capacitative coupling. Alternatively the coupling may be by a sliding contact, for example with brushes. A tuned circuit may be electrically connected to at least one of the electrodes, for example the tuned circuit may be connected between one electrode and ground potential. For example a tuned circuit may comprise an inductor connected to the capacitative coupling to one electrode and to ground potential, the tuned circuit preferably resonating at a frequency substantially that of the supply. The tuned circuit may be a matching network.
Each rotary die may be substantially cylindrical, and rotate about a fixed axis of rotation. Alternatively each rotary die may be of substantially polygonal cross-section, for example octagonal, the axes of rotation being sprung loaded towards each other. The dies may be arranged to form one capsule at a time, forming the multiplicity of recesses in succession as the dies rotate. Alternatively the dies may be arranged to form a plurality of capsules at once, side-by-side across the width of the films. A heater may be associated with the rotary dies, to provide heating of the films to soften them, before they are deformed to form the recesses. The films may be deformed by suction into matching recesses in the dies. The cutting out of the capsules may be performed by punching, but alternatively the dies may be sufficiently close together, at least around the periphery of each recess, that the film surrounding each capsule is sufficiently thin that the capsules can be easily pushed out of the remaining web; for example around the periphery of each capsule the film might be of a thickness between 10 and 20 xcexcm.
The filling material may be a pharmaceutical, and is a preferably a liquid. Where the capsules are intended to be swallowed (for example where they contain a pharmaceutical or a nutritional supplement), the polymeric material should be ingestible. It may for example be gelatin, or a water-soluble cellulose derivative. For example it may be hydroxypropyl methyl cellulose, which is approved for use with pharmaceuticals and in food (being indicated by the code E464 in Europe). Other suitable polymeric materials would be edible seaweed-derived polymers such as sodium alginate (E401), propylene glycol alginate (E405) or agarxe2x80x94agar (E406). The polymeric material must not contain any harmful or toxic additives, but may contain compounds such as glycerol (E422) or glycerol monostearate (E471) as plasticisers, these compounds also being ingestible and dispersible or soluble in water. Other suitable cellulose derivatives are hydroxypropyl cellulose (E463), and methyl ethyl cellulose (E465). There is no requirement for any water to be added to the film, and indeed it is preferable that the films should be at least superficially dry, that is to say in equilibrium with ambient conditions. For example the film might be in equilibrium with air at a temperature of 25xc2x0 C. and a relative humidity of 40%. For example, it might be stored before use in a controlled humidity environment, with a relative humidity preferably in the range 30% to 70%. Under such circumstances the film would evidently incorporate some water but would appear completely dry, and such incorporated water would tend to act as a plasticiser.
The invention also provides an apparatus for making and filling capsules by the method specified above, comprising rotary dies arranged to deform the film and to dielectrically weld them together. In a further aspect, the invention provides a capsule formed by the method or apparatus of the invention.